Attenuating effects of Azanza garckeana fractions on glycemo-impaired-associated dyslipidemia, hepatopathy, and nephropathy.

OBJECTIVES: The use of medicinal plants for diabetes treatment is increasing owing to their effectiveness and safety compared to synthetic drugs. Thus, the ameliorative effects of Azanza garckeana (F. Hoffm.) fractions in diabetes-induced dyslipidemia, hepatopathy, and nephropathy in rats were evaluated in this study. METHODS: Rats with alloxan (120 mg/kg body weight (BW))-induced diabetes were randomized into different groups (n=5) and treated with the crude methanolic extract, and fractions (n-hexane, ethyl acetate, and aqueous fractions) of A. garckeana each at 100, 200, and 400 mg/kg BW. Glibenclamide (5 mg/kg BW) was used as a reference drug, and all treatments were administered orally daily for 6 weeks. RESULTS: Our data revealed that treatment with the crude extract caused a dose-dependent hypoglycemic effect of 61.32±3.45%, 76.05±3.05%, and 78.59±5.90% at 100, 200, and 400 mg/kg BW, respectively and improved the BW of the animals. The extract also ameliorated the elevated cholesterol, triglyceride, low-density lipoprotein cholesterol, and increased serum levels of high-density lipoprotein cholesterol compared with untreated control animals. The extract also reversed serum biochemical alterations in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, total and direct bilirubin, urea, and uric acid that were observed in untreated diabetic rats. Interestingly, the A. garckeana fraction also exhibited significant protection against diabetes-induced dyslipidemia, hepatopathy, and nephropathy in rats, with the ethyl acetate fraction exhibiting a remarkable protective effect. The LC-MS characterisation of the active fraction identified the presence of various phenolic and flavonoid compounds that could be responsible for the bioactivity of the fraction. CONCLUSION: Collectively, this study suggests the potential application of A. garckeana for effective treatment of diabetic nephropathy, with the ethyl acetate fraction of this plant representing a reserve of potential candidates for developing new drugs.

Platelet Rich Plasma and Adipose-Derived Mesenchymal Stem Cells Mitigate Methotrexate-Induced Nephrotoxicity in Rat via Nrf2/Pparγ/HO-1 and NF-Κb/Keap1/Caspase-3 Signaling Pathways: Oxidative Stress and Apoptosis Interplay.

BACKGROUND: the nephrotoxicity of methotrexate (MTX) is observed in high-dose therapy. Moreover, low-dose MTX therapy for rheumatic diseases is debatable and claimed to cause renal impairment. This study aimed at studying the effect of methotrexate in repeated low doses on rat kidneys and assessing the efficacy of adipose-derived mesenchymal stem cells (AD-MSCs) and platelet rich plasma (PRP) for attenuating this effect. METHODS: Forty-two male Wistar rats were used, 10 rats were donors of AD-MSCs and PRP, 8 rats served as control, and the remaining rats were subjected to induction of nephrotoxicity by MTX intraperitoneal injection once weekly for successive 8 weeks and then assigned into 3 groups of 8 animals each: Group II: received MTX only. Group III: received MTX + PRP. Group IV: received MTX + AD-MSCs. After one month, rats were anaesthetized, serum-sampled, and renal tissue removed for biochemical, histological, and ultrastructural evaluation. RESULTS: there was significant tubular degeneration, glomerulosclerosis, fibrosis, decreased renal index, along with increased levels of urea and creatinine in the MTX group compared to the control group. Immunohistochemical expression of caspase-3 and iNOS in the renal tissue was significantly increased in group II compared to groups III and IV. Biochemical results revealed higher tissue malondialdehyde (MDA) concentration in the MTX-injected group which decreased significantly in co-treatment with either AD-MSC or PRP + MTX. MSC promoted the activation of the Nrf2/PPARγ/HO-1 and NF-κB/Keap1/caspase-3 pathways, increased antioxidant enzyme activities, reduced lipid peroxidation levels, and alleviated oxidative damage and apoptosis. PRP showed therapeutic effects and molecular mechanisms similar to MSC. Furthermore, MSC and PRP treatment significantly reduced MTX-induced upregulation of the pro-inflammatory (NF-κB, interleukin-1ß, and TNF-α), oxidative stress (Nrf-2, hemoxygenase-1, glutathione, and malondialdehyde), and nitrosative stress (iNOS) markers in the kidney. CONCLUSION: repeated administration of low-dose MTX resulted in massive renal tissue toxicity and deterioration of renal function in rats which proved to be attenuated by PRP and AD-MSCs through their anti-inflammatory, anti-apoptotic and anti-fibrotic properties.

Prospective single-center study of chronic myeloid leukemia in chronic phase: switching from branded imatinib to a copy drug and back.

Imatinib (Glivec(®)/Gleevec(®)) has shown long-term efficacy and safety in randomized trials. No large-scale studies have prospectively assessed the benefit-risk profile of an imatinib copy drug. We prospectively evaluated the response of patients with chronic myeloid leukemia in chronic phase in one institution. Patients with a complete hematologic response (n = 126) switched from branded imatinib to an imatinib copy drug. Subsequently, all patients switched back to the branded imatinib. Many patients in this study had a loss of hematologic response and tolerability issues with the imatinib copy drug. Hematologic response and tolerability improved upon retreatment with branded Glivec.

Middle ear and hearing disorders of schoolchildren aged 7-10 years in South Sinai, Egypt.

Hearing loss among schoolchildren in developing countries is reported to be a significant health problem. Data on child hearing loss in South Sinai, a remote governorate of Egypt, are lacking. Middle ear diseases and hearing impairment were assessed among 453 primary-school children aged 7-10 years in South Sinai (906 ears). Otoscopic examination, tympanometry and pure tone audiometry (PTA) were done. Ear disease was found in 27.5% of the ears examined. The commonest cause was secretory otitis media (10.8%), followed by occluded earwax (9.5%). Mild and moderate hearing loss affected 8.5% of the sample, while sensorineural hearing loss affected 2.4%; only 0.4% had moderate and severe hearing loss. Hearing impairment affects 19.3% of this age group in South Sinai. None of the children with hearing impairment had been previously diagnosed or was receiving treatment and support. Hearing and middle ear screening at schools is recommended for early detection and management of middle ear and hearing problems.

Middle ear and hearing disorders of schoolchildren aged 7-10 years in South Sinai, Egypt

Hearing loss among schoolchildren in developing countries is reported to be a significant health problem. Data on child hearing loss in South Sinai, a remote governorate of Egypt, are lacking. Middle ear diseases and hearing impairment were assessed among 453 primary-school children aged 7-10 years in South Sinai [906 ears]. Otoscopic examination, tympanometry and pure tone audiometry [PTA] were done. Ear disease was found in 27.5% of the ears examined. The commonest cause was secretory otitis media [10.8%], followed by occluded earwax [9.5%]. Mild and moderate hearing loss affected 8.5% of the sample, while sensorineural hearing loss affected 2.4%; only 0.4% had moderate and severe hearing loss. Hearing impairment affects 19.3% of this age group in South Sinai. None of the children with hearing impairment had been previously diagnosed or was receiving treatment and support. Hearing and middle ear screening at schools is recommended for early detection and management of middle ear and hearing problems